Discriminative Accuracy of Plasma Phospho-tau217 for Alzheimer Disease vs Other Neurodegenerative Disorders

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

There are limitations in current diagnostic testing approaches for Alzheimer disease (AD).

Related collections

Most cited references 34

Record: found
Abstract: not found
Article: not found

Comparing the Areas under Two or More Correlated Receiver Operating Characteristic Curves: A Nonparametric Approach

David DeLong, Elizabeth Delong, Daniel L Clarke-Pearson (1988)

0 comments Cited 2756 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease

Clifford R. Jack, David Bennett, Kaj Blennow … (2018)

In 2011, the National Institute on Aging and Alzheimer’s Association created separate diagnostic recommendations for the preclinical, mild cognitive impairment, and dementia stages of Alzheimer’s disease. Scientific progress in the interim led to an initiative by the National Institute on Aging and Alzheimer’s Association to update and unify the 2011 guidelines. This unifying update is labeled a “research framework” because its intended use is for observational and interventional research, not routine clinical care. In the National Institute on Aging and Alzheimer’s Association Research Framework, Alzheimer’s disease (AD) is defined by its underlying pathologic processes that can be documented by postmortem examination or in vivo by biomarkers. The diagnosis is not based on the clinical consequences of the disease (i.e., symptoms/signs) in this research framework, which shifts the definition of AD in living people from a syndromal to a biological construct. The research framework focuses on the diagnosis of AD with biomarkers in living persons. Biomarkers are grouped into those of β amyloid deposition, pathologic tau, and neurodegeneration [AT(N)]. This ATN classification system groups different biomarkers (imaging and biofluids) by the pathologic process each measures. The AT(N) system is flexible in that new biomarkers can be added to the three existing AT(N) groups, and new biomarker groups beyond AT(N) can be added when they become available. We focus on AD as a continuum, and cognitive staging may be accomplished using continuous measures. However, we also outline two different categorical cognitive schemes for staging the severity of cognitive impairment: a scheme using three traditional syndromal categories and a six-stage numeric scheme. It is important to stress that this framework seeks to create a common language with which investigators can generate and test hypotheses about the interactions among different pathologic processes (denoted by biomarkers) and cognitive symptoms. We appreciate the concern that this biomarker-based research framework has the potential to be misused. Therefore, we emphasize, first, it is premature and inappropriate to use this research framework in general medical practice. Second, this research framework should not be used to restrict alternative approaches to hypothesis testing that do not use biomarkers. There will be situations where biomarkers are not available or requiring them would be counterproductive to the specific research goals (discussed in more detail later in the document). Thus, biomarker-based research should not be considered a template for all research into age-related cognitive impairment and dementia; rather, it should be applied when it is fit for the purpose of the specific research goals of a study. Importantly, this framework should be examined in diverse populations. Although it is possible that β-amyloid plaques and neurofibrillary tau deposits are not causal in AD pathogenesis, it is these abnormal protein deposits that define AD as a unique neurodegenerative disease among different disorders that can lead to dementia. We envision that defining AD as a biological construct will enable a more accurate characterization and understanding of the sequence of events that lead to cognitive impairment that is associated with AD, as well as the multifactorial etiology of dementia. This approach also will enable a more precise approach to interventional trials where specific pathways can be targeted in the disease process and in the appropriate people.

0 comments Cited 2606 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Neuropathological stageing of Alzheimer-related changes

H Braak, E Braak (1991)

Eighty-three brains obtained at autopsy from nondemented and demented individuals were examined for extracellular amyloid deposits and intraneuronal neurofibrillary changes. The distribution pattern and packing density of amyloid deposits turned out to be of limited significance for differentiation of neuropathological stages. Neurofibrillary changes occurred in the form of neuritic plaques, neurofibrillary tangles and neuropil threads. The distribution of neuritic plaques varied widely not only within architectonic units but also from one individual to another. Neurofibrillary tangles and neuropil threads, in contrast, exhibited a characteristic distribution pattern permitting the differentiation of six stages. The first two stages were characterized by an either mild or severe alteration of the transentorhinal layer Pre-alpha (transentorhinal stages I-II). The two forms of limbic stages (stages III-IV) were marked by a conspicuous affection of layer Pre-alpha in both transentorhinal region and proper entorhinal cortex. In addition, there was mild involvement of the first Ammon's horn sector. The hallmark of the two isocortical stages (stages V-VI) was the destruction of virtually all isocortical association areas. The investigation showed that recognition of the six stages required qualitative evaluation of only a few key preparations.

0 comments Cited 1865 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Title: JAMA

Abbreviated Title: JAMA

Publisher: American Medical Association (AMA)

ISSN (Print): 0098-7484

Publication date (Electronic): July 28 2020

Affiliations

[1 ]Clinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden

[2 ]Memory Clinic, Skåne University Hospital, Malmö, Sweden

[3 ]Massachusetts General Hospital, Harvard Medical School, Boston

[4 ]Grupo de Neurociencias de Antioquia of Universidad de Antioquia, Medellin, Colombia

[5 ]Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden

[6 ]Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden

[7 ]Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, United Kingdom

[8 ]UK Dementia Research Institute at UCL, London, United Kingdom

[9 ]Banner Alzheimer’s Institute, Phoenix, Arizona

[10 ]Banner Sun Health Research Institute, Sun City, Arizona

[11 ]Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden

[12 ]Department of Neurology, Skåne University Hospital, Lund, Sweden

[13 ]Molecular Neuropathology of Alzheimer’s Disease (MoNeA), Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

[14 ]Eli Lilly and Company, Indianapolis, Indiana

[15 ]University of Arizona, Phoenix

[16 ]Arizona State University, Phoenix

[17 ]Translational Genomics Research Institute, Phoenix, Arizona

Article

DOI: 10.1001/jama.2020.12134

PMC ID: 7388060

PubMed ID: 32722745

SO-VID: 0e0c598f-355d-4d59-ab0a-d5567e5f1f0f

History

Data availability:

Comments

Comment on this article

scite_

Cited by 384

See all cited by

Most referenced authors 910

See all reference authors

- Version 1

Discriminative Accuracy of Plasma Phospho-tau217 for Alzheimer Disease vs Other Neurodegenerative Disorders

Read this article at

Abstract

Related collections

UCL: UN SDG 03 Good Health and Well-Being

Most cited references 34

Comparing the Areas under Two or More Correlated Receiver Operating Characteristic Curves: A Nonparametric Approach

NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease

Neuropathological stageing of Alzheimer-related changes

Author and article information

Journal

Affiliations

Article

History

Comments

Comment on this article

Similar content 2,803

Cited by 384

Most referenced authors 910